Prostate cancer continues to be a leading cause of cancer-related death in the United States. Identifying the means for preventing the disease and establishing its earlier diagnosis are essential for reducing mortality from prostate cancer and are, therefore, of utmost importance. This project will test the hypothesis that serial measurement of prostate specific antigen (PSA) is an intermediate marker for prostate cancer. It will also test, in a pair of ongoing randomized, double-blind cancer prevention trials using the micronutrient selenium (Sc), the hypothesis that Se supplementation reduces the incidence of either serially increasing PSA levels or prostate cancer. The design of this study is ambi-directional. The retrospective portion will measure PSA levels in the frozen serum samples of 1,000 men in the ongoing cancer prevention trials. Three PSA levels will be determined and subjects with positive PSA levels (a PSA of >4.0 ng/ml or an annual positive trend of >0.75 ng/ml) will be referred for follow up and the resultant documentation will be obtained. The prospective portion will consist of two cohorts:with a total of 1,000 men from the two cancer prevention trials from the low Sc areas of the U.S. The combination of these two cohorts will provide for a wide distribution of plasma Sc levels. The first cohort will have semi-annual PSA, Sc, for a wide distribution of plasma Sc levels. The first cohort will have semi-annual PSA, Sc, micronutrients, testosterone, and prolactin measurements. Subject with positive PSA levels will be referred for follow up and the resultant documentation will be obtained. An estimated 250 cases of elevated PSA levels and 101 cases of prostate cancer will be reported in eh course of this study. These numbers will afford this project the statistical power to detect a 30% reduction in the median time to failure for PSA and a 42% reduction in median time to failure for prostate cancer, in a two-tailed test at 80% power and an alpha=.05.